Vasodilator effect of angiotensin-(1–7) in mature and sponge-induced neovasculature

Machado, R. D. P.; Ferreira, Mônica Alves Neves Diniz; Belo, Andrezza V.; Santos, Robson A.S.; Andrade, Sílvia Passos

doi:10.1016/s0167-0115(02)00070-8

Cited by 17 publications

(17 citation statements)

References 31 publications

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“…These data are consistent with the recent observations from Machado et al (31) showing that ANG-(1-7) acts as vasodilator in a mice model of sponge-induced neovascularization as well as in normal cutaneous vascular beds. The absence of significant alterations on the spleen, muscle, and lung indicates the ANG-(1-7) selectivity and suggests the involvement of tissue-specific signaling mechanisms in its effects.…”

Section: Discussionsupporting

confidence: 93%

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Systemic and regional hemodynamic effects of angiotensin-(1–7) in rats

Sampaio

Nascimento

Santos

2003

American Journal of Physiology-Heart and Circulatory Physiology

175

135

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The systemic and regional hemodynamics effects of ANG-(1-7) were examined in urethane-anesthetized rats. The blood flow distribution (kidneys, skin, mesentery, lungs, spleen, brain, muscle, and adrenals), cardiac output, and total peripheral resistance were investigated by using fluorescent microspheres. Blood pressure and heart rate were recorded from the brachial artery. ANG-(1-7) infusion (110 fmol ⅐ min Ϫ1 ⅐ 10 min Ϫ1 iv) significantly increased blood flow to the kidney (5.10 Ϯ 1.07 to 8.30 Ϯ 0.97 ml ⅐ min Ϫ1 ⅐ g Ϫ1 ), mesentery (0.73 Ϯ 0.16 to 1.17 Ϯ 0.49 ml ⅐ min Ϫ1 ⅐ g Ϫ1 ), brain (1.32 Ϯ 0.44 to 2.18 Ϯ 0.85 ml ⅐ min Ϫ1 ⅐ g Ϫ1 ), and skin (0.07 Ϯ 0.02 to 0.18 Ϯ 0.07 ml ⅐ min Ϫ1 ⅐ g Ϫ1 ) and the vascular conductance in these organs. ANG-(1-7) also produced a significant increase in cardiac index (30%) and a decrease in total peripheral resistance (2.90 Ϯ 0.55 to 2.15 Ϯ 0.28 mmHg ⅐ ml Ϫ1 ⅐ min ⅐ 100 g). Blood flow to the spleen, muscle, lungs, and adrenals, as well as the blood pressure and heart rate, were not altered by the ANG-(1-7) infusion. The selective ANG-(1-7) antagonist A-779 reduced the blood flow in renal, cerebral, mesenteric, and cutaneous beds and blocked the ANG-(1-7)-induced vasodilatation in the kidney, mesentery, and skin, suggesting a significant role of endogenous ANG-(1-7) in these territories. The effects of ANG-(1-7) on the cerebral blood flow, cardiac index, systolic volume, and total peripheral resistance were partially attenuated by A-779. A high dose of ANG-(1-7) (11 pmol ⅐ min Ϫ1 ⅐ 10 min Ϫ1 ) caused an opposite effect of that produced by the low dose. Our results show for the first time that ANG-(1-7) has a previously unsuspected potent effect in the blood flow distribution and systemic hemodynamics. regional blood flow; fluorescent microspheres ANGIOTENSIN-(1-7), a bioactive component of the renin-angiotensin system, is formed in the circulation and various tissues from ANG I or ANG II through ANG-converting enzyme (ACE)-dependent and independent pathways (11,48,51). The recent discovery of the ANG-(1-7)-forming enzyme ACE2 adds a potentially new dimension to the ANG-(1-7) formation and favors the possibility that this peptide acts like a true paracrine hormone (9, 56). Interestingly, although the ACE pathway predominantly metabolizes ANG-(1-7) (11, 51), this peptide inhibits the ACE C-domain (3, 8), and as a result, increased levels of ANG-(1-7) observed during ACE inhibition may have an important participation in the cardiovascular effects produced by this therapy (24, 25,51).The actions of ANG-(1-7) are either complementary or distinct from those of ANG II. Actually, the accumulating evidence indicates that ANG-(1-7) exerts mainly a counterregulatory role within the renin-ANG system (11,46,48).The blood vessels are an important site for the opposing actions of ANG II and ANG-(1-7). Vascular responses to ANG-(1-7) significantly differ from those induced by ANG II. In blood vessels, ANG-(1-7) acts mainly as a vasodilator and antiproliferative hormone (16,48,51). It has been s...

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Section: Discussionsupporting

confidence: 93%

“…The CO was increased by 30%, which can be explained, at least in part, by the decrease in TPR (ϳ26%). The potent and selective effect of ANG-(1-7) in several territories confirms and extends previous observations (17,31,35,36,41,45).…”

Section: Discussionsupporting

confidence: 90%

Systemic and regional hemodynamic effects of angiotensin-(1–7) in rats

Sampaio

Nascimento

Santos

2003

American Journal of Physiology-Heart and Circulatory Physiology

175

135

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“…Studies from our laboratory documented that ANG-(1-7) reverses neointimal growth induced by denudation of the vascular endothelium of a carotid artery (29) through a non-AT 1 /AT 2 receptor (16). Additional antiangiogenic effects of ANG-(1-7) were documented in a mouse sponge model of angiogenesis, whereby ANG-(1-7) inhibited vessel formation within the implant (24,25). There is evidence that ANG-(1-7) contributes to the antihypertensive effect produced by blockers of the RAS because blockade of ANG-(1-7) receptors with a selective receptor antagonist or a selective ANG-(1-7) antibody reversed the antihypertensive effect mediated by chronic administration of lisinopril and losartan in rats (22).…”

Section: Discussionmentioning

confidence: 97%

Angiotensin II AT₁ receptors regulate ACE2 and angiotensin-(1–7) expression in the aorta of spontaneously hypertensive rats

Igase¹,

Strawn²,

Gallagher³

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

199

165

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When increased in vascular tissues, angiotensin-converting enzyme 2 (ACE2), a carboxypeptidase that hydrolyzes angiotensin II to angiotensin-(1-7), may augment the growth inhibitory and vasodilatory effects of the heptapeptide. We investigated the regulation of ACE2 and angiotensin-(1-7) expression in aortas and carotid arteries of 12-wk-old male spontaneously hypertensive rats (SHR) by determining the effect of sustained angiotensin type 1 (AT 1) receptor blockade with olmesartan (10 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 , n ϭ 13) compared with those that received atenolol (30 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 , n ϭ 13), hydralazine (10 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 , n ϭ 13), or vehicle (n ϭ 21). Systolic blood pressures were ϳ30% lower (P Ͻ 0.05) in rats treated for 2 wk with olmesartan compared with vehicletreated rats. Both atenolol and hydralazine produced similar decreases in systolic blood pressure. ACE2 mRNA in the thoracic aorta of olmesartan-treated rats (n ϭ 8) was fivefold greater (P Ͻ 0.05) than that in vehicle-treated rats (n ϭ 16), whereas atenolol (n ϭ 8) or hydralazine (n ϭ 8) had no effect. Immunostaining intensities in rats treated with olmesartan (n ϭ 5) were also associated with increased (P Ͻ 0.05) ACE2 and angiotensin-(1-7) in thoracic aorta media compared with vehicle-treated rats. In contrast, immunostaining intensities for both ACE2 and angiotensin-(1-7) were not different from vehicle (n ϭ 5) in carotid arteries of SHR medicated with either atenolol (n ϭ 5) or hydralazine (n ϭ 5). A comparison of vessel wall dimensions showed that olmesartan selectively reduced the thoracic aorta media-to-lumen ratio (P Ͻ 0.05) and media thickness (P Ͻ 0.05) without an effect on carotid artery morphometry. Compared with vehicle-treated SHR, vascular hypertrophy determined from media and lumen measurements was not changed in SHR given either atenolol or hydralazine. These data represent the first report of ACE2 and angiotensin-(1-7) expression in the aorta and carotid arteries of SHR. Increased ACE2 and angiotensin-(1-7) in association with altered dimensions of the thoracic aorta but not carotid arteries in response to olmesartan treatment provides evidence that this pathway is regulated by AT1 receptors and may be important in mediating the pressure-independent vascular remodeling effects of angiotensin peptides.angiotensin-converting enzyme 2; angiotensin type 1 receptor; vascular remodeling ANGIOTENSIN-CONVERTING ENZYME (ACE)2 is a newly recognized ACE homolog within the renin-angiotensin system (RAS) that is produced and secreted from a variety of cell types (19). Although ACE2 may act on several substrates, it exhibits high catalytic efficiency specifically for the hydrolysis of ANG II into the vasodilator and growth inhibitor heptapeptide angiotensin-(1-7) [ANG-(1-7)] (7, 13, 15). In previous experiments, we showed that ANG-(1-7) mediates the vasodilator effects of combined ACE inhibition and angiotensin type 1 (AT 1 ) receptor blockade (22). Furthermore, a continuous intravenous infusion of ANG-(1-7) reduced neointimal growth in caroti...

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“…It was suggested that the antiangiogenic effect of ANG-(1-7) in the mouse sponge model of angiogenesis is associated with NO release by activation of an ANG receptor distinct from AT 1 and AT 2 (Machado et al, 2001). In preexisting (skin) and newly formed vasculature (14-day-old polyurethane sponge implants) in mice, ANG-(1-7)-induced vasodilator effects was prevented by the specific receptor antagonist (D-Ala 7 )-ANG-(1-7) and abolished by NOS inhibitors, suggesting that this peptide contributes to the vasodilatation via NO also in newly formed vascular beds (Machado et al, 2002). ANG-(1-7) and AVE 0991 released NO and superoxide anions from bovine aortic endothelial cells, the effect being inhibited by a selective ANG-(1-7) antagonist, and an AT 2 antagonist inhibited AVE 0991-stimulated NO production but had no inhibitory effect on superoxide production (Wiemer et al, 2002).…”

Section: Angiotensin-(1-7)-induced Vasodilatationmentioning

confidence: 97%

Interaction of Endothelial Nitric Oxide and Angiotensin in the Circulation

2007

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Vasodilator effect of angiotensin-(1–7) in mature and sponge-induced neovasculature

Cited by 17 publications

References 31 publications

Systemic and regional hemodynamic effects of angiotensin-(1–7) in rats

Systemic and regional hemodynamic effects of angiotensin-(1–7) in rats

Angiotensin II AT₁ receptors regulate ACE2 and angiotensin-(1–7) expression in the aorta of spontaneously hypertensive rats

Interaction of Endothelial Nitric Oxide and Angiotensin in the Circulation

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Vasodilator effect of angiotensin-(1–7) in mature and sponge-induced neovasculature

Cited by 17 publications

References 31 publications

Systemic and regional hemodynamic effects of angiotensin-(1–7) in rats

Systemic and regional hemodynamic effects of angiotensin-(1–7) in rats

Angiotensin II AT1 receptors regulate ACE2 and angiotensin-(1–7) expression in the aorta of spontaneously hypertensive rats

Interaction of Endothelial Nitric Oxide and Angiotensin in the Circulation

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Angiotensin II AT₁ receptors regulate ACE2 and angiotensin-(1–7) expression in the aorta of spontaneously hypertensive rats